Structural highlights
Function
[FAE_METEA] Catalyzes the condensation of formaldehyde with tetrahydromethanopterin (H(4)MPT) to 5,10-methylenetetrahydromethanopterin, a reaction which also proceeds spontaneously, but at a lower rate than that of the enzyme-catalyzed reaction. Is an essential enzyme for methylotrophic energy metabolism and formaldehyde detoxification of this bacterium.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Tetrahydromethanopterin (H4 MPT) is a tetrahydrofolate analogue involved as a C1 carrier in the metabolism of various groups of microorganisms. How H4MPT is bound to the respective C1 unit converting enzymes remained elusive. We describe here the structure of the homopentameric formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1 established at 2.0 angstrom without and at 1.9 angstrom with methylene-H4MPT bound. Methylene-H4MPT is bound in an "S"-shaped conformation into the cleft formed between two adjacent subunits. Coenzyme binding is accompanied by side chain rearrangements up to 5 angstrom and leads to a rigidification of the C-terminal arm, a formation of a new hydrophobic cluster, and an inversion of the amide side chain of Gln88. Methylene-H4MPT in Fae shows a characteristic kink between the tetrahydropyrazine and the imidazolidine rings of 70 degrees that is more pronounced than that reported for free methylene-H4MPT in solution (50 degrees). Fae is an essential enzyme for energy metabolism and formaldehyde detoxification of this bacterium and catalyzes the formation of methylene-H4MPT from H4MPT and formaldehyde. The molecular mechanism ofthis reaction involving His22 as acid catalyst is discussed.
How an enzyme binds the C1 carrier tetrahydromethanopterin. Structure of the tetrahydromethanopterin-dependent formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1.,Acharya P, Goenrich M, Hagemeier CH, Demmer U, Vorholt JA, Thauer RK, Ermler U J Biol Chem. 2005 Apr 8;280(14):13712-9. Epub 2005 Jan 4. PMID:15632161[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vorholt JA, Marx CJ, Lidstrom ME, Thauer RK. Novel formaldehyde-activating enzyme in Methylobacterium extorquens AM1 required for growth on methanol. J Bacteriol. 2000 Dec;182(23):6645-50. PMID:11073907
- ↑ Acharya P, Goenrich M, Hagemeier CH, Demmer U, Vorholt JA, Thauer RK, Ermler U. How an enzyme binds the C1 carrier tetrahydromethanopterin. Structure of the tetrahydromethanopterin-dependent formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1. J Biol Chem. 2005 Apr 8;280(14):13712-9. Epub 2005 Jan 4. PMID:15632161 doi:http://dx.doi.org/10.1074/jbc.M412320200
- ↑ Acharya P, Goenrich M, Hagemeier CH, Demmer U, Vorholt JA, Thauer RK, Ermler U. How an enzyme binds the C1 carrier tetrahydromethanopterin. Structure of the tetrahydromethanopterin-dependent formaldehyde-activating enzyme (Fae) from Methylobacterium extorquens AM1. J Biol Chem. 2005 Apr 8;280(14):13712-9. Epub 2005 Jan 4. PMID:15632161 doi:http://dx.doi.org/10.1074/jbc.M412320200
